What is the interaction between Buspirone (an anxiolytic) and Mirtazapine (a tetracyclic antidepressant)?

From the Guidelines

Buspirone and mirtazapine can be used together to treat anxiety and depression, but their combination should be closely monitored by a healthcare provider due to the potential risk of serotonin syndrome, as suggested by the most recent evidence 1. When considering the use of buspirone and mirtazapine together, it's essential to understand their individual mechanisms and effects. Buspirone is an anti-anxiety medication that affects serotonin receptors in the brain, typically prescribed at 5-15 mg twice daily, with dosages sometimes reaching 60 mg daily in divided doses 1. Mirtazapine, on the other hand, is an atypical antidepressant that works through multiple mechanisms, affecting both serotonin and norepinephrine systems while also blocking histamine receptors, commonly prescribed at 15-45 mg once daily at bedtime due to its sedating effects 1. The combination of buspirone and mirtazapine may be beneficial for patients with both anxiety and depression, as they can address both conditions simultaneously. However, it's crucial to monitor for potential side effects, such as serotonin syndrome, which can be life-threatening. Other side effects of buspirone include dizziness and headaches, while mirtazapine commonly causes sedation, increased appetite, and weight gain 1. According to the most recent evidence, the combination of buspirone and mirtazapine is not significantly different from other treatment strategies in terms of efficacy, but it may have a lower risk of adverse events compared to other medications 1. The healthcare provider should carefully weigh the benefits and risks of using buspirone and mirtazapine together and closely monitor the patient's response to the treatment, as suggested by the evidence 1. Some key points to consider when using buspirone and mirtazapine together include:

• Starting with a low dose of buspirone and gradually increasing as needed and tolerated
• Monitoring for signs of serotonin syndrome, such as agitation, confusion, and changes in blood pressure
• Regularly assessing the patient's response to treatment and adjusting the dosage or medication as needed
• Gradually tapering the medication when discontinuing to avoid withdrawal symptoms
• Considering alternative treatment strategies if the patient experiences adverse events or does not respond to the treatment, as suggested by the evidence 1.

From the FDA Drug Label

Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with mirtazapine tablets increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases If serotonin syndrome occurs, consider discontinuation of mirtazapine tablets and/or concomitant serotonergicdrugs Examples SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, amphetamines, St. John’s Wort, tramadol, tryptophan, buspirone

The use of buspirone with mirtazapine may increase the risk of serotonin syndrome. Patients should be monitored for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consideration should be given to discontinuing mirtazapine and/or buspirone 2.

From the Research

Buspirone and Mirtazapine

• Buspirone is an azapirone derivative and a 5-HT1A partial agonist, used for the treatment of generalized anxiety disorder 3.
• It has anxiolytic properties similar to those of benzodiazepines, but with increased safety and lack of dependency-producing aspects 3.
• Buspirone is also efficacious for depression, either alone or together with an antidepressant drug, and for treating adverse sexual effects 4.
• Mirtazapine is an antidepressant that has been shown to be effective in individuals with depression and comorbid physical conditions, with a moderate to high efficacy and tolerability profile 5.
• There is no direct comparison between buspirone and mirtazapine in the provided studies, but both have been shown to be effective in treating anxiety and depression 3, 4, 5.

Treatment of Anxiety and Depression

• Buspirone is effective for treating generalized anxiety, but not other anxiety disorders 4.
• Mirtazapine has been shown to be effective in treating depression, with a moderate to high efficacy and tolerability profile 5.
• Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a modest advantage over bupropion in the treatment of anxious depression 6.
• The combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) has been shown to be effective in treating youth with depression and anxiety 7.

Comparison of Antidepressants

• Mirtazapine has been shown to be effective in treating depression, with a moderate to high efficacy and tolerability profile 5.
• SSRIs have been shown to have a modest advantage over bupropion in the treatment of anxious depression 6.
• Sertraline and paroxetine have been shown to be effective for the largest number of ICD-11 disease subgroups, with a moderate to high efficacy and tolerability profile 5.